Acid-Base regulation II Flashcards by Joel Glotfelty

The effectiveness of respiratory compensation for metabolic acidosis is limited to several days at best. This is because lowering PCO2 has what effects?

Increases pH, reduces renal HCO3- reabsorption (which then lowers plasma HCO3-)

Net effect is as if no compensation has occurred at all

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Predicted respiratory compensation for metabolic acidosis is a

1.5 mmHg drop in PCO2 per 1 meq/L decrease in HCO3-

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Useful to determine whether or not appropriate respiratory compensation to metabolic acidosis has occurred versus the presence of a second (respiratory) based acid-base disorder

Winter’s Formula

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Using Winter’s formula, if the calculated and measured PCO2 values are equal than we know that

Appropriate compensation is occuring

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Using Winter’s formula, if the measured PCO2 is greater than the calculated PCO2, than we know there is either

Respiratory acidosis too or no compensation

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Is a PCO2 of 40 mmHg in the presence of a metabolic acidosis normal?

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With a chronic metabolic acidosis, any PCO2 value significantly above what Winter’s predicts would indicate a

Co-existing respiratory acidosis

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With a chronic metabolic acidosis, a measured PCO2 less than calculate by Winter’s formula reveals the presence of co-existing

Respiratory alkalosis

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A normal pH with abnormal ABGs should immediately raise suspicion of a

Mixed acid-base disorder

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The final compensatory mechanism for metabolic acidosis is via the

Renal acidification of urine

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Assuming the kidneys are functioning normally, this process can begin within about 24 hours and is maximal at approximately

5-6 days

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Renal compensation for metabolic acidosis predominantly involves enhanced elimination of

NH4+ (as NH4Cl)

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As an example of the effectiveness of the kidneys in handling an increased acid load, a reduction of plasma HCO3- by only 4-5 meq/L can result in a

4-fold increase in NH4+ excretion over several days

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Determined by calculating the difference between the predominant plasma cation (Na+) and the sum of the most abundant plasma anions (HCO3- and Cl-)

Anion gap (AG)

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The normal range for AG is

7-16 meq/L

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The AG is simply the difference between

Unmeasured cations - unmeasured anions

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Accounts for the majority of unmeasured anions

Negative charges within proteins

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Therefor, an increased gao can result from a fall in unmeasured cations, or (most often) an increase in

Unmeasured anions

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An important unmeasured anion to note is

Albumin

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In the case of hemoconcentration, where the concentration of albumin is increased, the anion gap would be

Elevated

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In the event of hypoalbuminemia, for every 1g/dL drop in plasma albumin, AG should be adjusted downward by

2.5 meq/L

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The accumulation of certain anions can occur during various types of

Metabolic acidoses

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Elevated AG ALWAYS strongly suggests the presence of

Metabolic acidosis

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Duringmetabolic acidosis, and in the absence of unmeasured anions, lost HCO3- is replaced in order to maintain electroneutrality. What replaces it?

Cl-

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This normal anion gap metabolic acidosis is often referred to as

Hyperchloremic metabolic acidosis

Common with normal AG metabolic acidosis

Hyperchloremia

HCl + NaHCO3 → NaCl + H2CO3 → CO2 + H2O In this example, what is the result of loss of NaHCO3 due to a GI pathology?

Metabolic acidosis from increase in HCL due to loss of NaHCO3- HCl is buffered by remaining HCO3- which results in increased Cl- Results is hyperchloremia with normal AG

However, if H+ were to combine with an unmeasured anion, than what would happen?

AG would be elevated

With this in mind, it is not unusual for plasma chloride to be lowered with an

AG metabolic acidosis

It is important to note that increased AG is not exclusive to metabolic acidosis and can occur during

Metabolic alkalosis

The main factors contributing to this are

1. ) ECV depletion (contraction alkalosis) causing increased plasma [albumin] 2. ) Increase lactate production

Can occur in compensation for alkalemia

Increased lactate production

Lactic acid, ketoacids, salicylic acid, oxalic acid, glycolic acid, and formic acid each carry negative charges, and will each induce an abnormal rise in

AG (causing metabolic acidosis)

ANother way to show the relationships between anionic acid accumulation and HCO3- loss

delta-delta difference

By convention, we set basal HCO3- to

By convention, we set the normal AG to be

What is the delta-delta difference?

dd = Measured AG + measured [HCO3-] - 36

If dAG - dHCO3- = 0 than there is a single acid-base disorder which is

Metabolic acidosis

If there is a 1:1 correlation between dAG and dHCO3-, i.e. dAG - dHCO3- = 0 +/- 5 than we have

Ketoacidosis

We have to calculate the dd difference in a different manner for -due to the way lactate is cleared by the kidneys

Lactic acidosis

When we calculate dd diference during lactic acidosis, we know there is a SINGLE metabolic acid-base disorder if the value falls within

0 +/- 5

With the aforementioned in mind, dd values less than -5 warrant investigation for the presence of a

Mixed AG metabolic acidosis w/ non-AG metabolic acidosis

If dd is greater than 5, than we likely have a mixed

Metabolic acidosis with metabolic alkalosis

A mixed metabolic acidosis and metabolic alkalosis can occur during severe diabetic ketoacidosis where marked elevated ketones induce

Vomiting

Derived from pyruvic acid mostly from the processes of glycolysis or the deamination of alanine

Lactic acid (lactate + H+)

Lactic acid is buffered by HCO3- to yield lactate, which is subsequently metabolized into

Pyruvate

Pyruvate can then be further metabolized into

CO2 + H2O or glucose

Either metabolic pathway results in the generation of new

HCO3-

The catalysis of lactate requires its entry into the mitochondria and oxidative metabolism, processes which each require sufficient

Thus, if O2 delivery is blocked, we can see the accumulation of

Lactic acid

Common causes are poor tissue perfusion leading to impaired oxidation and ischemia, such as what results from cardiac arrest, shock, severe exercise, alcoholism, and many other pathologies

O2 delivery blockages that results in lactic acid buildup

During starvation, or perceived starvation, increased lipolysis results in an overabundance of

Free fatty acids delivered to the liver

Results in elevated serum glucagon and low serum insulin

Starvation

Caused by a lack of insulin or insulin resistance

Perceived starvation

In the face of this barrage, hepatic function resets leading to the preferential metabolism of FFA into

Ketoacids (rather than the preferred triglycerdies)

Signs of hyperglycemia with ketones in the urine correlate with

Diabetic ketoacidosis

Is measured as the difference between major urinary cations (Na+ and K+) and the major urinary anion (Cl-)

Urine AG

How do we calculate urine AG?

UAG = UNa + UK - UCl

Under normal conditions, urine AG will be at or very close to

Zero

Urine AG can be useful in discerning the cause of

Normal AG metabolic acidosis

Not useful with elevated AG acidosis

Urine AG

The most common cause of normal AG metabolic acidosis (due to GI loss of HCO3-)

Diarrhea

When pH drops, the kidneys will excrete H+ in the form of

NH4+

This so-called acidification of urine occurs in the distal portions of the structures known as - Where urine is being formed - Called distal acidification

Nephrons

Excreted with H+ in order to maintain electroneutrality

Cl-

Thus, if the kidneys are doing their job in response to metabolic acidosis, excreted urine will contain a lot of Cl- and this drives

Urine AG to negative values

A negative AG is usually in the range of

-20 to -50 meq/L

Acidoses that result from the inability of the kidneys to properly acidify urine

Renal Tubule Acidoses (RTA)

In an RTA, because H+ is not effectively cleared by the kidneys, the ratio of plasma HCO3-/H+ decreases and pH drops, thus forming a

Metabolic acidosis

Since these kidneys are sick, they can not excrete the excess H+, which means they will not excrete Cl- either, and this drives

Urine AG to positive values

An elevation in plasma [HCO3-] due to H+ loss

Metabolic alkalosis

Caused by diarrhea, antacid therapy, hypovolemia, vomiting, and nasogastric suction

Metbolic alkalosis

Contraction alkalosis around a set amount of HCO3- -A concern with diuretic usage

Hypovolemia

The maintenance of metabolic alkalosis usually involves a defect in renal HCO3- secretion and excretion due to

Effective volume depletion and Cl- loss

Impeded due to excess HCO3-

Cl- resorption from the kidneys

The kidneys respond to volume depletion by increasing the reabsorption of

Na+

This process is mediated by

Aldosterone and An-II

In the context of volume depletion and metabolic alkalosis, An-II stimulates

Aldosterone secretion

An-II also acts with the kidneys to stimulate the

Proximal Na+/H+ exchanger and the Na+/HCO3- symporter

Remember that H+ secretion equates to

HCO3- reabsorption by the kidneys

Thus with elevated An-II, K+ secretion is upregulated (via aldosterone) and HCO3- reabsorption is

Directly enhanced

Signs of hypokalemia and hypochloremia often accompany

Metabolic alkalosis

To be more specific, to compensate for volume depletion, the kidneys attempt to increase the resorption of

Na+ and Cl-

It is important to understand that this process is coupled. In other words

There is a 1:1 ratio between Na+ resorption and Cl- resorption

With reduced Cl-, Na+ resorption can only occur at the expense of

K+ and H+ secretion

H+ secretion equates to increased HCO3- resorption and the alkalosis can be exacerbated by

K+ loss

In order to compensate for metabolic alkalosis, pH must be lowered , and this is accomplished via -opposite of what is seen in metabolic acidosis

Decreased ventilation

In acid-base disturbances, we can see shifts between H+ and the most abundant intracellular cation

K+

There is a connection between metabolic alkalosis and

Hypokalemia

At the cellular level, increased extracellular pH (low [H+]) results in? -The reason hypokalemia is associated with metabolic alkalosis

H+ translocating from cells to ECF. This is offset by K+ moving from ECF into cells. Thus ECF [K+] is decreased and we can see hypokalemia

How does hypokalemia result in metabolic alkalosis?

Low K+ causes K+ to move from cells to ECF. To maintain electroneutrality, H+ then moves from ECF into cells and the result is an increased pH

Abnormally increased K+ excretion may induce metabolic alkalosis, and hypokalemia actually promotes

Renal H+ secretion

The trade-off for H+ secretion is the generation and absorption of

HCO3-

Volume contraction, diminished glomerular filtration rate, and aldosterone excess often accompany

Metabolic alkalosis

Renal H+ secretion is stimulated by which three things?

1. ) Aldosterone excess 2. ) Hypovolemia 3. ) Hypokalemia

How does acidosis result in hyperkalemia?

Acidosis impairs renal tubular K+ secretion and K+ excretion is diminished. Increased extracellular H+ causes H+ to move into cells which results in K+ moving to the ECF to maintain electroneutrality

Hyperkalemia and acidosis are often coupled because hyperkalemia suppresses

H+ secretion from kidneys